Biological Significance of Anti–SARS-CoV-2 Antibodies
Lessons Learned From Progressive Multifocal Leukoencephalopathy
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Abstract
Objective To discuss the pathogenic and diagnostic relevance of cellular and humoral immune responses against severe acute respiratory syndrome novel coronavirus (SARS-COV-2) and pertinent observations made in progressive multifocal leukoencephalopathy (PML).
Methods Review of pertinent literature.
Results There is at least 1 precedent for an antibody response against a viral pathogen that fails to provide host protection in the absence of immune-competent CD4+ T cells. PML is an infection of the CNS caused by JC virus (JCV), which commonly occurs during treatment with the therapeutic monoclonal antibody natalizumab. In this context, the humoral immune response fails to prevent JCV reactivation, and elevated anti-JCV serum indices are associated with a higher PML incidence. The more relevant immune-competent cells in host defense against JCV appear to be T cells. T cell–mediated responses are also detectable in convalescing patients with SARS-COV-2 irrespective of the humoral immune response.
Conclusion Based on pathogenic lessons learned from PML under natalizumab therapy, we suggest the incorporation of functional assays that determine neutralizing properties of SARS-CoV-2–specific antibodies. In addition, we outline the potential role of T-cell detection assays in determining herd immunity in a given population or in studying therapeutic responses to vaccines.
Glossary
- GMFR=
- geometric mean fold rise;
- GMT=
- geometric mean titer;
- Ig=
- immunoglobulin;
- IRIS=
- immune reconstitution inflammatory syndrome;
- JCV=
- JC virus;
- PML=
- progressive multifocal leukoencephalopathy
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by UT Southwestern Medical Center.
- Received August 13, 2020.
- Accepted in final form November 9, 2020.
- Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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